Field of the Invention
The present invention relates to an antibody or antigen binding fragment thereof, that binds to TM4SF5 (transmembrane 4 superfamily member 5 protein), a nucleic acid molecule encoding thereof, a recombinant vector, a transformant and a preparation method of the antibody therefrom, and uses of the antibody.
Description of the Related Art
The mRNA expression of TM4SF5 (transmembrane 4 superfamily member 5 protein) in human cancer is prevalently observed in pancreatic cancer, soft tissue sarcoma, gastric cancer, carcinoma of the papilla vateri, and colon cancer (Muller-Pillasch F, et al. Gene 208, 25-30(1998)). TM4SF5 plays an important role in hepatocellular carcinoma (HCC) formation by induced morphological elongation and epithelial-mesenchymal transition, and caused abnormal cell growth in multilayers in vitro and tumor formation in vivo (Lee S A, et al. J Clin Invest 118, 1354-1366(2008); Lekishvili T, et al. J Cell Sci 121, 685-694(2008)). It is reported that TM4SF5 expression-induced uncontrolled cell proliferation and angiogenesis was provoked by inhibition of integrin α2 function in collagen type I environment by extracellular interaction between TM4SF5 and integrin α2 (Lee S A, et al. Carcinogenesis 30, 1872-1879(2009)). A synthetic inhibitor targeting TM4SF5, 4′-(p-toluenesulfonyl-amido)-4-hydroxychalcone (TSAHC), has been shown to inhibit HCC growth and metastasis formation in vitro and in vivo (Lee S A, et al. Hepatology 49, 1316-1325(2009)). Therefore, a role for the TM4SF5 in HCC formation represents a novel molecular target for the clinical development of HCC therapeutics.
HCC is one of the most common cancers globally, and widespread especially in Asia and sub-Saharan Africa. It is reported that the development of most HCC is a multistep process including dysplastic nodule, early HCC, well-differentiated HCC, and moderately and poorly differentiated HCCs (Forner A, et al. Lancet 379, 1245-1255(2012)).
Colon cancer is the third most common cancer in the world, and it is more common in developed countries than undeveloped countries. The most commonly mutated genes in colon cancer are APC, β-catenin, AXIN1, AXIN2, TCF7L2, or NKD1 which are involved in the Wnt-APC-β-catenin signaling pathway (Korinek V, et al. Science 275, 1784-1787(1997); Khan N P, et al. Mol Cell Biochem 355, 149-155(2011); Folsom A R, et al. Diabetes Care 31, 905-909(2008); Guo J, et al. PLoS One 4, e7982(2009)).
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.